Summary of work: This project focuses on the mechanism involved in regulating the binding of oxygen to hemoglobin and the transport of oxygen to the tissues. Emphasis is placed on ways in which these functions are impaired and change with age. These studies have focused on the oxidation of hemoglobin, which produces nonfunctional hemoglobin and the simultaneous release of oxyradicals. The enhancement of these oxidative processes under hypoxic conditions is being explored as a possible source of tissue and organ damage, which would be exacerbated during aging. Studies are also included which are directed at the stability of the entire erythrocyte and the erythrocyte membrane. Animal and human studies are performed to investigate possible functional impairment associated with red cell damage. Erythrocyte nitric oxide is being studied as a measure of nitric oxide synthesis and in order to oxplore the possible role of the erythrocyte in regulating blood flow by releasing nitric oxide. The interaction of amyloids with the erythrocyte is being investigated to determine whether the red cell plays a role in the transport of amyloids and in amyloid induced oxidative stress.